Method and device for intermittent occlusion of a vein draining the organ system

ABSTRACT

In a method for the intermittent occlusion of a vein draining the organ system, in which the vein is occluded by an occlusion device, the fluid pressure in the occluded vein is continuously measured and stored, the behavior of the fluid pressure is determined as a function of time, and the occlusion of the vein is triggered and/or released as a function of at least one characteristic value derived from the pressure measurements, pressure is applied during the occlusion in a pulsating manner. The device for the intermittent occlusion of a vein, including an occlusion device, a pressure measuring device for continuously measuring the fluid pressure in the occluded vein, and a memory for storing the fluid pressure behavior as a function of time, means are provided for applying a pulsating pressure in the occluded vein.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of U.S. application Ser. No. 13/437,325 filed onApr. 2, 2012, now U.S. Pat. No. 8,500,623,which is a continuation ofU.S. application Ser. No. 12/312,794 filed on May 27, 2009, now U.S.Pat. No. 8,162,813,which is a National Stage application under 35 U.S.C.§371 and claims benefit under 35 U.S.C. §119(a) of InternationalApplication No. PCT/AT2007/000543 filed on Nov. 30, 2007, which claimsthe benefit of Austrian Application Serial No. A1999/2006 filed on Nov.30, 2006, and all of these aforementioned disclosures are incorporatedby reference in their entirety into this application.

TECHNICAL FIELD

The invention relates to a method for the intermittent occlusion of avein draining the organ system, in which the vein is occluded by anocclusion device, the fluid pressure in the occluded vein iscontinuously measured and stored, the behavior of the fluid pressure isdetermined as a function of time, and the occlusion of the vein istriggered and/or released as a function of at least one characteristicvalue derived from the pressure measurements, and to a device forcarrying out said method. The veins concerned, for instance, include thejugular vein and the coronary sinus.

BACKGROUND

Arterial blood, which supplies the heart muscle, is able to pass throughhealthy heart tissue while nourishing the same, yet has difficultyreaching ischemic tissue. As a result, the supply of ischemic tissuewith nutrients and the discharge of metabolic catabolites from suchischemic tissue will be impaired.

In this context, it has already been proposed to supply the ischemictissue with blood through retrograde perfusion. In doing so, attemptshave been made to allow the blood to flow back from the coronary sinusthrough the coronary venous system in counterflow by feeding blood froma different source into the coronary sinus, either by permanentlyconnecting an artery with the coronary sinus or by temporarily insertinga catheter into the sinus, which catheter is supplied with blood takenfrom a remote artery and transported by the aid of a blood pump locatedoutside the patient's body.

The initially proposed technique for retroperfusion uses an inflatableballoon fixed to the end of a catheter to intermittently occlude thecoronary sinus. The blood pressure in the coronary sinus rises duringthe occlusion at every heart beat so as to cause blood reaching thecoronary sinus through the healthy tissue of the heart muscle to beflushed back into the ischemic tissue. For such an intermittent coronarysinus occlusion, the balloon end of the catheter is inserted eitherpercutaneously or surgically. The other end of the catheter is suppliedwith a gas or fluid by a pump which causes the cyclic inflation anddeflation of the balloon.

A typical application of blood retroinfusion in coronary veins by theintermittent occlusion of the coronary sinus applies to myocardialprotection during a short-term coronary arterial occlusion in thecontext of a cardiologic intervention. A typical such intervention, forinstance, includes the balloon dilatation of an arterioscleroticallyconstricted coronary artery. That method, which is also known aspercutaneous transluminal coronary angioplasty (PTCA), comprises theconduction of a balloon catheter into the region of the coronary arterystenosis under X-ray control and the compression of the arterioscleroticplaque by the inflation of the balloon located on the end of thecatheter. During the dilatation of the balloon, no supply of the tissuewith oxygen-containing blood takes place downstream in the artery, withfunctional changes in the ischemic area of the myocard being detectablealready at dilatations lasting longer than 30 seconds. Problems involvedin the ischemic protection of the myocard will also be faced in otherinterventions aimed at coronary vascularization such as, e.g.,atherectomy, coronary endoprostheses, laser applications andpercutaneous surgeries of the cardiac valves.

A device for the retroinfusion of coronary veins has, for instance,become known from EP 230 996 A2, by which a pressure-controlledintermittent coronary sinus occlusion can be performed. The devicecomprises a means for occluding the sinus such as, e.g., an inflatableballoon catheter, a pressure measuring unit for measuring the fluidpressure within the coronary sinus and a control unit which generatestriggering signals for the occlusion device to trigger or release anocclusion. The control unit is devised in a manner that the pressuremaximum in the coronary sinus is measured during every heart beat, aplateau value of the pressure maxima of consecutive heart beats isestimated by calculation and the occlusion of the coronary sinus isreleased on the basis of the plateau value of the pressure maxima.

The occlusion of the coronary sinus causes a pressure increase and,subsequently, a retroperfusion of blood via the respective vein into thenutritive capillaries of the ischemic area so as to enable the supply ofnutrients to that area. At a release of the occlusion, the retroperfusedblood is flushed out while the metabolic waste products are carried offat the same time.

In a series of investigations, it could be demonstrated that endothelialgrowth factors inter alia respond to the application of mechanical loadsand, in particular, pressure. While the blood is passing through thevessels, the endothelium basically is acted upon not only by shearingforces but, naturally, also by the initially mentioned pressures,whereby a pressure increase lasting for as long as possible will, inprinciple, lead to an increased release of vessel-forming genes (VEGFgenes, vascular endothelial growth factor encoding genes), which will bebeneficial to the regeneration of the heart vessels and, in particular,neoangiogenesis. It is, however, not possible to achieve an indefinitelylong lasting pressure increase by an occlusion using known methods,since the occlusion must again be intermittently released after havingreached the plateau value, thus causing the pressure to be loweredagain.

SUMMARY

The invention now aims to enhance the contribution to neoangiogenesisbased on a pressure increase or changing pressure sensitivity and toimprove these effects theoretically recognized as positive. To solvethis object, the method according to the invention, departing from theinitially described method, essentially consists in that pressure isapplied during the occlusion in a pulsating manner. It could beexperimentally demonstrated that a linear pressure increase as well asthe mere shearing stress of the endothelium contribute considerably lessto the production of vascular endothelial growth factors, and hence toneoangiogenesis. It is only by the pulsating application of pressureproposed by the invention that this effect will be improved, wherein itis essential in this connection that said pulsating pressure be appliedduring the occlusion and, hence in the phase in which a pressurebuild-up is generally effected until the achievement of a plateau value.In a particularly advantageous manner, the method according to theinvention is carried out in that the pulsating pressure build-up isapplied pneumatically or hydraulically via an oscillating, pulsatingmembrane, in particular a further balloon, or piezoelectrically, wherebypressure waves at frequencies of between 50 and 250 per minute and, inparticular, 100 to 200 per minute are introduced. In principle, thefrequency of these pressure waves preferably is to be chosen higher thanwhat would correspond to the pulse rate of a grownup human. Therelatively high pulse rates of 100 to 200 per minute largely correspondto pulse rates as are observed in newborns and, in particular, duringthe development phase of the heart. Such pulse rates have turned out tobe of particular advantage for angioneogenesis. In a particularlyadvantageous manner, the method is carried out such that the pressurewave maxima are synchronized with ECG signals, heart tones and/or phasictemperature changes in the blood flow.

The device according to the invention for the intermittent occlusion ofa vein, including an occlusion device, a pressure measuring device forcontinuously measuring the fluid pressure in the occluded vein, and amemory for storing the fluid pressure behavior as a function of time, isessentially characterized in that means are provided for applying apulsating pressure in the occluded vein. A device of this type issuitable for carrying out the method according to the invention, themeans for applying said pulsating pressure being, as a rule, arranged inthe occluded portion of the vein distally of the occlusion device.

In a preferred manner, the means for applying a pulsating pressure arecomprised of an oscillating body, said oscillating body being drivableto form pressure waves. Such an oscillating body is able to induce theformation of pressure waves according to different principles, saidoscillating body in a preferred manner being arranged in a cage designedin the manner of a stent. The cage preferably provided in connectionwith said device, in the manner of a stent provides security to theregion in which the oscillating body is to enter into effect, thuspreventing a direct collision of the oscillating body with the vesselwall. In this manner, the desired pulsating pressure waves can beefficiently built up with little mechanical expenditure, the pressurebuild-up being basically achievable by various mechanical converters. Inthis respect, a configuration in which the oscillating body is comprisedof a pneumatically or hydraulically expandable hollow body or balloon isparticularly preferred.

In order to ensure that the higher-frequency pulsations also result inaccordingly elevated pressure peak values, with the stimulation of theendothelium thus being effected in the desired manner, the configurationis advantageously devised such that the oscillating body is coupled withthe occlusion device and additionally drivable to pulsations during thetime of the occlusion-related pressure build-up.

With the initially mentioned device, a pressure measuring device isbasically employed in such a manner that, after having estimated therespective plateau value occurring as a result of an occlusion, theappropriate relief of the balloon is also effected and the occlusion isreleased again. This measurement is, however, irrelevant to the actualsuccess of the pulsating pressure such that appropriate control is notreadily feasible. The configuration is, therefore, advantageouslydevised such that the pressure measuring device is designed to measurethe fluid pressure in the occluded coronary sinus and to measure thepressure peaks introduced by the oscillating body.

In a preferred manner, the configuration is devised such that the meansfor applying a pulsating pressure is comprised of a device for thepulsating introduction of perfusate into the occluded vein. Such aconfiguration not only enables the generation of the desired pressurewaves, but in addition renders feasible the use of, for instance, freshblood for nourishing the ischemic tissue, whereby even blood lost fromthe bloodstream at another location during an intervention can becompensated for.

In a particularly advantageous manner, the device according to theinvention is further developed such that a device controlling theformation of said pressure waves is arranged to generate pressure wavesfrom a lower threshold value of the detectable pressure increase afterthe occlusion and to stop the generation of pressure waves upon releaseof the occlusion. To synchronize the pressure wave maxima with relevantparameters for the circulatory function, the configuration is preferablydevised such that a device controlling the formation of said pressurewaves is connectable with signal lines for ECG signals, heart tonesand/or temperature measurements.

The device according to the invention is advantageously furtherdeveloped to the effect that the formation of said pressure waves isinducible as a function of the blood pressure peaks produced by theheart. The formation of pressure waves can thus be synchronized with theoccurrence of blood pressure peaks so as to enable the retrogradeperfusion of the ischemic tissue in a particularly effective manner withlittle expenditure.

In a preferred manner, the formation of pressure waves is inducible by afluid pulsingly conveyed within the lumen. Such a pneumatically drivenconfiguration is characterized by a simple handling and a particularlydirect response characteristic. In a preferred manner, the formation ofsaid pressure waves can, moreover, be induced by sonic waves and, inparticular, ultrasonic waves, as well as by electromechanical and, inparticular, nanoelectromechanical waves, as in correspondence with apreferred embodiment of the device according to the invention. In thismanner, pressure waves of virtually any frequency can be generated.

According to a preferred embodiment, the device according to theinvention is further developed to the effect that the formation of saidpressure waves is inducible by a combination of the action of theocclusion device and the action of the means for applying a pulsatingpressure in the vein. In this manner, the occlusion device can be usedto generate pressure waves in addition to the means for applying apulsating pressure, thus enabling the formation of especially strongpressure waves.

DESCRIPTION OF DRAWINGS

In the following, the invention will be explained in more detail by wayof an exemplary embodiment illustrated in the drawing.

Therein, FIG. 1 is a diagrammatic view of a heart with a device for theintermittent occlusion of the coronary sinus; and

FIG. 2 is an enlarged illustration of the distal end of the catheteraccording to the invention.

DETAILED DESCRIPTION

FIG. 1 schematically depicts the device for the intermittent occlusionof the coronary sinus, wherein a multi-lumen catheter 1 is shown, whosedistal end 2 is inserted in the coronary sinus of the heart 3 via theatrium. The proximal end 4 of the catheter 1 has a balloon inflationlumen 5 connected with a pump 6. The pressure prevailing on the distalend 2 of the catheter 1 is detected by a pressure measuring device 7,the latter also including a memory for the measured values acquired. Therespectively measured pressure values are fed to a control device 8including a calculation unit, which delivers control signals via line 9for starting and stopping the pump 6.

FIG. 2 illustrates the distal end 2 of the multi-lumen catheter 1 on anenlarged scale. The balloon inflation lumen in this case runs into theballoon 10, which is shown in FIG. 2 in the expanded and hence occludingposition. The distal end is secured by a stent-like cage 11, which canbe pressed onto the vessel wall 12 so as to avoid any direct collisionof said end with the aorta or vessel wall. The distal end, besides theballoon 10, now also carries a vibrator body 13, to which hydraulicpressure pulses can be fed, for instance through lumen 14. During theocclusion, i.e. with the balloon 10 inflated, pressure medium is thuspulsingly introduced into the vibrator body 13 via lumen 14 so as toobtain the respective pressure change load by the thus enhancedstimulation of the factors triggering neoangiogenesis.

What is claimed is:
 1. A method for intermittent occlusion of a coronarysinus, comprising the steps of: occluding a coronary sinus of a patientusing an occlusion device coupled to a distal end portion of themulti-lumen catheter and being in communication with a first lumen ofthe multi-lumen catheter, the occlusion device being adjustable betweena non-occluding state and an occluding state that is configured tosubstantially occlude the coronary sinus; measuring and storing fluidpressure values in the occluded coronary sinus during said occludingstep; during said occluding step, outputting a pulsating pressure intothe occluded coronary sinus from the distal end portion of themulti-lumen catheter positioned in the coronary sinus, wherein thepulsating pressure is output into the coronary sinus using pressurewaves at a frequency greater than a pulse rate of the patient, whereinsaid outputting the pulsating pressure into the occluded coronary sinuscomprise outputting the pulsating pressure from a pulsating deviceattached to the distal end portion of the multi-lumen catheter andpositioned in the coronary sinus, wherein said pulsating devicecomprises a pulsating membrane structure in communication with a secondlumen of the multi-lumen catheter, the pulsating membrane structurebeing positioned at least partially distal of the occlusion device; andreleasing the occlusion of the coronary sinus as a function of at leastone characteristic value derived from said pressure values in theoccluded coronary sinus.
 2. The method of claim 1, wherein saidoutputting the pulsating pressure occurs only during the occlusion ofthe coronary sinus when the occlusion device is in the occluding state.3. The method of claim 1, wherein said outputting the pulsating pressurecomprises applying the pulsating pressure pneumatically or hydraulicallyinto an interior space defined by the pulsating membrane structure. 4.The method of claim 1, wherein said outputting the pulsating pressureinto the occluded coronary sinus comprises outputting pressure wavesinto the occluded coronary sinus at a frequency between 50 and 250 perminute.
 5. The method of claim 1, wherein said outputting the pulsatingpressure into the occluded coronary sinus initiates at a lower thresholdvalue of a detectable pressure increase after the occlusion and thenstops upon release of the occlusion.
 6. The method of claim 1, whereinsaid releasing the occlusion of the coronary sinus includes adjustingthe occlusion device from the occluded state to the non-occluding state.7. A method for intermittent occlusion of a coronary sinus, comprisingthe steps of: occluding a coronary sinus of a patient using an occlusiondevice coupled to a distal end portion of the multi-lumen catheter andbeing in communication with a first lumen of the multi-lumen catheter,the occlusion device being adjustable between a non-occluding state andan occluding state that is configured to substantially occlude thecoronary sinus; measuring and storing fluid pressure values in theoccluded coronary sinus during said occluding step; during saidoccluding step, outputting a pulsating pressure into the occludedcoronary sinus from a pulsating membrane structure coupled to the distalend portion of the multi-lumen catheter and positioned in the coronarysinus, wherein the pulsating membrane structure outputs pressure wavesat a frequency greater than a pulse rate of the patient, releasing theocclusion of the coronary sinus as a function of at least onecharacteristic value derived from said pressure values in the occludedcoronary sinus.
 8. The method of claim 7, wherein said outputting thepulsating pressure into the occluded coronary sinus comprises applyingthe pulsating pressure pneumatically or hydraulically to the pulsatingmembrane structure.
 9. The method of claim 8, said outputting thepulsating pressure into the occluded coronary sinus comprises thepulsating membrane structure outputting pressure waves at the frequencybetween 50 and 250 per minute.
 10. The method of claim 7, wherein saidpulsating membrane comprises a distal balloon structure in communicationwith a second lumen of the multi-lumen catheter, the distal balloonstructure being positioned at least partially distal of the occlusiondevice.
 11. The method of claim 10, wherein said outputting thepulsating pressure comprises applying the pulsating pressurepneumatically or hydraulically into an interior space of the distalballoon structure.
 12. The method of claim 7, wherein the pulsatingmembrane structure is positioned the distal end portion of themulti-lumen catheter at least partially distal of the occlusion device.13. The method of claim 12, wherein said releasing the occlusion of thecoronary sinus includes adjusting the occlusion device from the occludedstate to the non-occluding state.
 14. The method of claim 7, whereinsaid outputting the pulsating pressure occurs only during the occlusionof the coronary sinus when the occlusion device is in the occludingstate.
 15. The method of claim 7, wherein said outputting the pulsatingpressure into the occluded coronary sinus initiates at a lower thresholdvalue of a detectable pressure increase after the occlusion and thenstops upon release of the occlusion.